Study of the 482G/A variation in PGC-1alpha gene domain MEF2C as possible mechanism of type 2 diabetes / 中华医学遗传学杂志
Chinese Journal of Medical Genetics
; (6): 616-623, 2008.
Article
em Zh
| WPRIM
| ID: wpr-308007
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of the 482G/A polymorphism of the PGC-1alpha gene with type 2 diabetes by family-based study in the Han population in South China, and to analyze the quantitative and qualitative binding force changes between the PGC-1alpha domain mutant and MEF2C, as well as to evaluate the possibility of PGC-1alpha -MEF2C-GLUT4 pathway in the pathogenesis of type 2 diabetes.</p><p><b>METHODS</b>Blood samples were collected from 350 patients with type 2 diabetes and their first-degree relatives. Genomic DNA was extracted and polymorphic PGC-1alpha genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequencing. The results were analyzed by family-based transmission disequilibrium test (TDT) and haplotype relative risk (HRR). The protein-protein interaction between PGC-1alpha and MEF2C was detected by means of the site-directed mutagenesis kit and bacteriomatch two-hybrid system kit.</p><p><b>RESULTS</b>In the family-based study, HRR analyses demonstrated that the 482A allele was more often transmitted to patients than predicted by chance (chi (2)= 7.2170, P= 0.0072, HRR= 1.4496). TDT-extended test(ETDT) analyses also revealed that PGC-1alpha 482A allele was significantly deviated from 0.5 from heterozygous parents to patients than expected (219 trios, P= 0.0310; 350 trios, P= 0.0292). BacterioMatch Two-Hybrid System showed that 482A variation could lead to decreased binding force between PGC-1alpha and MEF2C (62.1+/- 8.97, P< 0.05).</p><p><b>CONCLUSION</b>The 482A polymorphism increases the risk of developing type 2 diabetic mellitus in the South China Han population, which might be mediated by the PGC-1alpha -MEF2C-GLUT4 pathway.</p>
Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Fatores de Transcrição
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Haplótipos
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Transdução de Sinais
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Etnicidade
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Modelos Logísticos
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Estrutura Terciária de Proteína
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Fatores de Regulação Miogênica
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Predisposição Genética para Doença
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Técnicas do Sistema de Duplo-Híbrido
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Polimorfismo de Nucleotídeo Único
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Qualitative_research
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
Zh
Revista:
Chinese Journal of Medical Genetics
Ano de publicação:
2008
Tipo de documento:
Article